Regulation of CAD gene expression in mouse fibroblasts during the transition from the resting to the growing state

Abstract

We have analyzed the steady-state levels of CAD mRNA and ATCase activity in BALB/c 3T3 mouse fibroblasts at quiescence and at various time points following the initiation of serum stimulation. Steady-state levels of CAD mRNA in 3T3 cells following 12 h of serum stimulation increased 10-fold over levels measured at quiescence. In contrast to the observed increase in steady-state levels of CAD mRNA, its rate of transcription increased only 3-fold, suggesting that the expression of CAD gene in these cells is regulated at both the transcriptional and post-transcriptional levels, to a major extent by the latter. These increases in CAD mRNA in serum-stimulated cells were followed by parallel increases in ATCase activity as well. When comparing DNA synthesis ([ 3H]thymidine uptake) to the accumulation of CAD mRNA and ATCase activity, it was observed that this accumulation occurred during the mid- to late-G 1 phase of the cell cycle. These results suggest that the expression of CAD gene is cell growth dependent and may be a prerequisite to DNA synthesis.